Investigating Endolysosomal Dysfunction in Two Ultra-Rare Hereditary Spastic Paraplegia Disorders via Immunofluorescence Confocal Microscopy

Hereditary Spastic Paraplegias (HSP) are a large, clinically and genetically heterogenous family of motor neurodegenerative disorders, characterized by corticospinal axonopathy which leads to progressive lower-limb spasticity and weakness. Current medical interventions only help to manage the symptoms rather than address their molecular causes. Elucidating the underlying pathological mechanisms is crucial in developing novel therapeutic treatments, and dysfunction of intracellular trafficking is emerging as an interesting target for HSP, as well as for other neurodegenerative disorders alike. With a focus on two ultra-rare forms of HSP -KIDINS220-dependent SINO and ALS2-dependent IAHSP- this investigation aims at exploring potential abnormalities of the endolysosomal pathway in patient-derived fibroblasts, through the use of immunofluorescence confocal microscopy.

Hereditary Spastic Paraplegias (HSP) are a large, clinically and genetically heterogenous family of motor neurodegenerative disorders. They are characterized by corticospinal axonopathy which leads to progressive lower-limb spasticity and weakness. Current medical interventions only help to manage the symptoms rather than address their molecular causes. Elucidating the underlying pathological mechanisms is crucial in developing novel therapeutic treatments, and dysfunction of intracellular trafficking is emerging as an interesting target. Endo-lysosomal trafficking has been well established as being essential to cellular homeostasis and naturally its dysfunction and/or dysregulation for HSP, as well as for other neurodegenerative disorders alike. With a focus on two ultra-rare forms of HSP -KIDINS220-dependent SINO and ALS2-dependent IAHSP- this investigation aims at exploring potential abnormalities of the endolysosomal pathway in patient-derived fibroblasts, through the use of immunofluorescence confocal microscopy.